Understanding How Cancer Can Relapse (Biology)

University of Missouri researchers discover a novel cell-to-cell communication network that helps tumors regrow following treatment.

In the fight against cancers, activating mutations in the RAS family of genes stand in the way of finding viable treatment options. Now, scientists at the University of Missouri and Yale University have discovered that one of these mutations — oncogenic RAS or RASV12 — is also responsible for the regrowth of cancer cells following genotoxic therapy treatment, or drugs that cause damage to a cancer cell’s DNA in order to eliminate it from the body.

“Most of our knowledge of how cells respond to DNA damage is mainly derived from studies looking at the single cell level,” said Yves Chabu, an assistant professor in the MU College of Arts and Science. “Therefore, we don’t know much about how tumor cells respond to DNA damage in the broader context of the tissue level, and what possible implications these responses might have on a tumor’s relapse following genotoxic therapies. To address this, we looked at how tissues containing patches of cells carrying oncogenic RAS mutations respond to DNA damage. We focused on oncogenic RAS because it is associated with cancers relapse and resistance to genotoxic therapies in humans. This approach has allowed us to identify novel cell-to-cell communication within the tissue that instructs tumor cells in tissues to regrow. It’s something we would not have identified if we were only looking at the single cell level.”

Genotoxic therapies eliminate cancer cells by causing DNA damage inside those cells. Cells normally will stop multiplying and attempt to repair this DNA damage in order to avoid elimination, but if the damage is too extensive the cell will abandon the repair process and trigger its own demise. Cells rely on a molecule called “p53” to execute these outcomes.

“We found that in oncogenic RAS tissues, cells elevate the levels of the p53 protein to varying degrees in response to DNA damage,” said Chabu, whose appointment is in the Division of Biological Sciences. “Further analyses revealed that cells with high p53 protein levels, or more extensive DNA damage, do not simply die in response to the DNA damage. Instead, they release a growth signal called interlukin-6 into the tumor environment. Interlinkin-6 instructs cells with low p53 levels, or cells with less DNA damage, to activate JAK/STAT, a growth-amplifying signal, and drive tumor regrowth after treatment. We essentially have a situation where cells that are vulnerable to the treatment are instructing the more robust cells to take over and grow.”

Chabu, who has been studying oncogenic RAS mutations for more than a decade, said their findings suggest that adding JAK/STAT inhibitors to genotoxic therapies will limit the ability of RAS tumors to regrow. He said another interesting aspect of their findings is that p53 is traditionally considered as a tumor suppressor protein.

“A loss of p53 activity, due to genetic mutation, causes cells to grow uncontrollably while accumulating even more DNA mutations,” Chabu said. “So, naturally one would think that having more p53 activity is a good thing because it prevents pre-cancerous cells from growing and forming cancers. Yet, here we find that too much of a normal, not mutated, p53 can signal the surrounding RAS tissues to overgrow.”

While scientists have been studying mutations in RAS genes for more than three decades, scientists today have a better understanding of how these mutant genes work. However, many of them still consider these mutations to be “undruggable” or resistant to therapeutic treatment, according to the National Cancer Institute.

The study, “Cooperation between oncogenic RAS and wild-type p53 stimulates STAT non-cell autonomously to promote tumor radioresistance,” was published in Communications Biology, a journal published by Nature Research. The work was supported in part by the Howard Hughes Medical Institute and start-up funds from the University of Missouri. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Featured image: Yves Chabu © University of Missouri

Provided by University of Missouri

Less Than A Nanometer Thick, Stronger And More Versatile Than Steel (Nanotechnology)

Scientists create stable nanosheets containing boron and hydrogen atoms with potential applications in nanoelectronics and quantum information technology.

What’s thinner than thin? One answer is two-dimensional materials — exotic materials of science with length and width but only one or two atoms in thickness. They offer the possibility of unprecedented boosts in device performance for electronic devices, solar cells, batteries and medical equipment.

In collaboration with Northwestern University and the University of Florida, scientists from the U.S. Department of Energy’s (DOE) Argonne National Laboratory report in Science magazine a breakthrough involving a 2D material called borophane, a sheet of boron and hydrogen a mere two atoms in thickness.

“We have tackled a significant challenge in determining the atomic structures from scanning tunneling microscopy images and computational modeling at the atomic scale with the help of computer vision.”

— Argonne’s Maria Chan, nanoscientist at the Center for Nanoscale Materials.

One of the most exciting developments in materials science in recent decades has been a 2D sheet of carbon (graphene), which is one atom thick and 200 times stronger than steel. A similarly promising and newer material is an atom-thick sheet of boron, called borophene — with an ​“e.” A multi-institutional team, including researchers in Argonne’s Center for Nanoscale Materials (a DOE Office of Science User Facility), first synthesized borophene in 2015.

While graphene is simply one atomic layer out of the many same layers in the common material graphite, borophene has no equivalent parent structure and is very difficult to prepare. What’s more, the rapid reaction of borophene with air means it is very unstable and changes form readily.

“Borophene by itself has all kinds of problems,” said Mark Hersam, Professor of Materials Science and Engineering at Northwestern University. ​“But when we mix borophene with hydrogen, the product suddenly becomes much more stable and attractive for use in the burgeoning fields of nanoelectronics and quantum information technology.”

The research team grew borophene on a silver substrate then exposed it to hydrogen to form the borophane. They then unraveled the complex structure of borophane by combining a scanning tunneling microscope with a computer-vision based algorithm that compares theoretical simulations of structures with experimental measurements. Computer vision is a branch of artificial intelligence that trains high performance computers to interpret and understand the visual world.

Even though the borophane material is only two atoms thick, its structure is quite complex because of the many possible arrangements for the boron and hydrogen atoms. ​“We have tackled a significant challenge in determining the atomic structures from scanning tunneling microscopy images and computational modeling at the atomic scale with the help of computer vision,” said Argonne’s Maria Chan, nanoscientist at the Center for Nanoscale Materials. Given the success in unraveling this complex structure, the team’s automated analytical technique should be applicable in identifying other complex nanostructures in the future.

“What is really encouraging from our results is that we found a borophane nanosheet on a silver substrate to be quite stable, unlike borophene,” said Pierre Darancet, nanoscientist at Argonne’s Center for Nanoscale Materials. ​“This means it should be easily integrated with other materials in the construction of new devices for optoelectronics, devices combining light with electronics.” Such light-controlling and light-emitting devices could be incorporated into telecommunications, medical equipment and more.

“These findings are an important step in realizing borophane’s incredible potential as a two-dimensional material for nanoelectronics,” Chan said.

The scientific paper reporting this work, entitled “Synthesis of borophane polymorphs through hydrogenation of borophene,” appeared in Science. Authors are Q. Li, V.S.C. Kolluru, M.S. Rahn, E. Schwenker, S. Li, R.G. Hennig, P. Darancet, M.K.Y. Chan and M.C. Hersam.

This work was supported by the Office of Naval Research, the National Science Foundation, DOE Office of Basic Energy Sciences, and Laboratory Directed Research and Development funding from Argonne.

Featured image: Structure of borophane sheet. Red, hydrogen; teal, boron. (Image by Qiucheng Li and Chaitanya Kolluru.)

Reference: Qiucheng Li, Venkata Surya Chaitanya Kolluru, Matthew S. Rahn, Eric Schwenker, Shaowei Li, Richard G. Hennig, Pierre Darancet, Maria K. Y. Chan, Mark C. Hersam, “Synthesis of borophane polymorphs through hydrogenation of borophene”, Science  12 Mar 2021: Vol. 371, Issue 6534, pp. 1143-1148 DOI: 10.1126/science.abg1874

Provided by Argonne National Laboratory

U of M Researchers Develop 99.9% Accurate Genetic Test For Early Detection of Palmer Amaranth (Agriculture)

Palmer Amaranth is a high-impact agronomic weed species that has cost the United States agriculture industry billions of dollars since its discovery outside of its native range in the southwestern U.S. and northwestern Mexico. Over the last 20 years, it has moved further north, and now poses a major threat to corn, soybean, and cotton growers across the south and Midwest regions of the United States.

It is not legal to sell any kind of seed in Minnesota if the seed lot contains Palmer Amaranth. The problem is this particular invasive species—which has shown potential to wipe out up to 91% of corn yields, 68% of soybean yields, and 54% of cotton yields— is difficult to visibly distinguish from other pigweed species, making identification reliant upon genetic testing.

In a recent study published in Pest Management Science, researchers from the University of Minnesota’s Minnesota Invasive Terrestrial Plants and Pests Center (MITPPC) and Colorado State University have developed a new test for identifying Palmer Amaranth that is more robust, easier to use, and — most importantly — has shown 99.9% accuracy. 

Due to rapid spread of herbicide resistance traits in Palmer populations, the prevention of Palmer establishment is more important than ever. Researchers hope to make the new test technology commercially available to agronomic professionals across the United States by the end of 2021, which can be applied to both individual samples and bulk seed mixes. 

“Development of tools and weed seed regulations play important roles, but ultimately it all comes back to the growers,” said lead author Anthony Brusa, a postdoctoral associate in the College of Food, Agricultural and Natural Resource Sciences. “Prevention of Palmer is a team effort. So far, every initial sighting of Palmer in Minnesota was from a grower, and control efforts wouldn’t be possible without their help.” 

To develop the test, researchers collected samples of Palmer Amaranth and related species from across the United States, as well as Mexico, South America and Africa. They then performed genomic sequencing on these samples and searched for specific genetic differences between species. The targets identified were then used to design a set of three genetic markers for the identification of Palmer DNA against the DNA of related pigweed species. Finally, those tests were validated for performance against the most robust testing panel assembled to date.

“We hope that this will be the first of many molecular diagnostics developed for weed seed testing,” said co-author Eric Patterson, an assistant professor and weed geneticist at Michigan State University. “The gates are open for developing tests for herbicide resistance, seed contamination, and seed bank diversity.” 

Accuracy for these markers ranged from 99.7%-99.9%, with only one-to-three errors against a panel of 1,250 samples. Bulk seed testing showed reliable detection of Palmer at a level of one Palmer seed in a mix of 200 pigweed seeds.

Genetic testing is necessary to identify which seed samples are Palmer Amaranth, and which are not. The newly-developed test is up to 99.9% accurate. © University of Minnesota

“We believe this has the potential to help prevent Palmer seed from being introduced as a contaminant in pollinator seed mixes, bird seed, and other seed lots sold from areas where Palmer is currently a problem, into areas like Minnesota,” said co-author Todd Gaines, an associate professor of molecular weed science at Colorado State University. “We also see great potential for this to be used to help protect corn and soybean exports by verifying the absence of Palmer in grain sold to countries that won’t accept Palmer-contaminated products.” 

In the immediate future, the research team continues to investigate novel approaches for Palmer control, and are currently investigating the potential use of genomic testing to identify Palmer presence in soil seed banks.

“The development of these new markers and their commercialization will provide new options to seed companies labeling seed for sale in Minnesota as well as other industries that may be at risk for introducing Palmer Amaranth via screenings, hay, equipment, or feed,” said Denise Thiede, section manager for seed, noxious weed, hemp, and biotechnology at the Minnesota Department of Agriculture. 

The research was funded by the Minnesota Invasive Terrestrial Plants & Pests Center through the Minnesota Environment and Natural Resources Trust Fund, and collaborators included University of Minnesota Extension, Colorado State University, Michigan State University, and the Minnesota Department of Agriculture.

Reference: Brusa, A., Patterson, E.L., Gaines, T.A., Dorn, K., Westra, P., Sparks, C.D. and Wyse, D. (2021), A needle in a seedstack: an improved method for detection of rare alleles in bulk seed testing through KASP. Pest Manag Sci. https://doi.org/10.1002/ps.6278

Provided by University of Minnesota

Maddening Itch Of Liver Disease Comes From A Surprising Source (Medicine)

Itching sensation originates in the skin cells themselves, after signaling from an excess of lipid

A devastating itching of the skin driven by severe liver disease turns out to have a surprising cause. Its discovery points toward possible new therapies for itching, and shows that the outer layer of the skin is so much more than insulation.

The finding, which appears April 2 in Gastroenterology, indicates that the keratinocyte cells of the skin surface are acting as what lead researcher Wolfgang Liedtke, MD PhD, calls ‘pre-neurons.’

“The skin cells themselves are sensory under certain conditions, specifically the outermost layer of cells, the keratinocytes,” said Liedtke, who is a professor of neurology at Duke School of Medicine.

This study on liver disease itching, done with colleagues in Mexico, Poland, Germany and Wake Forest University, is a continuation of Liedtke’s pursuit of understanding a calcium-permeable ion channel on the cell surface called TRPV4, which he discovered 20 years ago at Rockefeller University.

The TRPV4 channel plays a crucial role in many tissues, including the sensation of pain. It was known to exist in skin cells, but nobody knew why.

“The initial ideas were that it plays a role in how the skin is layered, and in skin barrier function,” Liedtke said. “But this current research is getting us into a more exciting territory of the skin actually moonlighting as a sensory organ.” Once a chemical signal of itching is received, keratinocytes relay the signal to nerve endings in the skin that belong to itch-sensing nerve cells in the dorsal root ganglion next to the spine.

“Dr. Liedtke and I had a longstanding interest in the role of TRPV4 in the skin, based on our previous collaborations we decided to focus on chronic itch,” said Yong Chen, and assistant professor of neurology at Duke who is first author on the study.

The researchers found that in a liver disease called primary biliary cholangitis (PBC), patients are left with a surplus of lysophosphatidylcholine (LPC) a phosphorylated lipid, or fat, circulating in the blood stream. They then demonstrated that LPC, injected into the skin of mice and monkeys, evokes itch.

Next they wanted to understand how this lipid could lead to the aggressive itching sensation. “If the itch comes up in PBC, it’s so debilitating that the patients might need a new liver. That’s how bad it can get,” Liedtke said. Importantly, the skin is not chronically inflamed in PBC, meaning there is debilitating itch in the absence of chronic skin inflammation.

The researchers found that when LPC reaches the skin, the lipid can bind directly to TRPV4. Once bound, it directly activates the ion channel to open the gate for calcium ions, which are a universal switch mechanism for many cellular processes.

But in this case, the signal does something surprising. The researchers followed a signaling cascade inside the cell in which one molecule hands off to another, resulting in the formation of a tiny bubble back on the skin cell’s surface called a vesicle. Vesicles are designed to bud off cells and carry whatever is inside them away.

In this case, the bubbles contained something surprising: micro-RNA, and it functioned as a signaling molecule. “This is crazy, because microRNAs are normally known to be gene regulators.” Liedtke said.

It turns out that this particular bit of microRNA is itself the signal that evokes the itch.

Once they had identified it as microRNA miR-146a, the researchers injected the molecule by itself into mice and monkeys and found that it immediately caused itching, not hours later, as it would if it were regulating genes.

“Future research will address which specific itch sensory neurons respond to miR-146a, beyond the TRPV1-dependent signaling that we have found, also its in-depth mechanism,” Chen said.

With the help of German and Polish liver specialists who have blood collections and itch data on PBC patients, the researchers discovered that the blood levels of microRNA-146a corresponded to itch severity, as did the LPC levels.  

Knowing all the parts of the signaling that leads from excess phospho-lipid, LPC, to intolerable itching gives scientists a new way to look for advanced liver disease markers, Liedtke said.

And it points to new avenues for treating the itch, either by possibly desensitizing the TRPV4 channels in skin with a topical treatment, attacking the specific microRNAs that drive the itch, or targeted depletion of LPC.

This research was supported by the US National Institutes of Health (DE018549, K12DE022793, R01DE027454), the Michael Ross Haffner Foundation (Charlotte, NC), Dirección General de Asuntos del Personal Académico (DGAPA)-Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) (IN200720); Consejo Nacional de Ciencia y Tecnología (CONACyT) (A1-S-8760) and Secretaría de Educación, Ciencia, Tecnología e Innovación del Gobierno de la Ciudad de México (SECTEI/208/2019).

Featured image: Excess lipids produced by liver failure signal an itching sensation directly to the skin cells, through a receptor called TRPV4 and a microRNA. (Wolfgang Liedtke)

Reference: “Epithelia-Sensory Neuron Crosstalk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine,” Yong Chen, Zi-Long Wang, Michele Yeo, Qiao-Juan Zhang, Ana E. López-Romero, Hui-Ping Ding, Xin Zhang, Qian Zeng, Sara L. Morales-Lázaro, Carlene Moore, Ying-Ai Jin, Huang-He Yang, Johannes Morstein, Andrey Bortsov, Marcin Krawczyk, Frank Lammert, Manal Abdelmalek, Anna Mae Diehl, Piotr Milkiewicz, Andreas E. Kremer, Jennifer Y. Zhang, Andrea Nackley, Tony E. Reeves, Mei-Chuan Ko, Ru-Rong Ji, Tamara Rosenbaum, Wolfgang Liedtke. Gastroenterology, April 2, 2021. DOI: 10.1053/j.gastro.2021.03.049

Provided by Duke University

UCF Study Shows Masks, Ventilation Stop COVID Spread Better than Social Distancing (Medicine)

The results indicate masks and proper ventilation may be key to allowing more capacity in schools, businesses and other indoor areas.

A new study from the University of Central Florida suggests that masks and a good ventilation system are more important than social distancing for reducing the airborne spread of COVID-19 in classrooms.

The research, published recently in the journal Physics of Fluids, comes at a critical time when schools and universities are considering returning to more in-person classes in the fall.

“The research is important as it provides guidance on how we are understanding safety in indoor environments,” says Michael Kinzel, an assistant professor in UCF’s Department of Mechanical and Aerospace Engineering and study co-author.

“The study finds that aerosol transmission routes do not display a need for six feet social distancing when masks are mandated,” he says. “These results highlight that with masks, transmission probability does not decrease with increased physical distancing, which emphasizes how mask mandates may be key to increasing capacity in schools and other places.”

In the study, the researchers created a computer model of a classroom with students and a teacher, then modeled airflow and disease transmission, and calculated airborne-driven transmission risk.

In the study, the researchers created a computer model of a classroom with students and a teacher, then modeled airflow and disease transmission, and calculated airborne-driven transmission risk. © UCF

The classroom model was 709 square feet with 9-foot-tall ceilings, similar to a smaller-size, university classroom, Kinzel says. The model had masked students — any one of whom could be infected— and a masked teacher at the front of the classroom.

The researchers examined the classroom using two scenarios — a ventilated classroom and an unventilated one — and using two models, Wells-Riley and Computational Fluid Dynamics. Wells-Riley is commonly used to assess indoor transmission probability and Computational Fluid Dynamics is often used to understand the aerodynamics of cars, aircraft and the underwater movement of submarines.

Masks were shown to be beneficial by preventing direct exposure of aerosols, as the masks provide a weak puff of warm air that causes aerosols to move vertically, thus preventing them from reaching adjacent students, Kinzel says.

Additionally, a ventilation system in combination with a good air filter reduced the infection risk by 40 to 50% compared to a classroom with no ventilation. This is because the ventilation system creates a steady current of air flow that circulates many of the aerosols into a filter that removes a portion of the aerosols compared to the no-ventilation scenario where the aerosols congregate above the people in the room.

These results corroborate recent guidelines from the U.S. Centers for Disease Control and Prevention that recommend reducing social distancing in elementary schools from six to three feet when mask use is universal, Kinzel says.

“If we compare infection probabilities when wearing masks, three feet of social distancing did not indicate an increase in infection probability with respect to six feet, which may provide evidence for schools and other businesses to safely operate through the rest of the pandemic,” Kinzel says.

“The results suggest exactly what the CDC is doing, that ventilation systems and mask usage are most important for preventing transmission and that social distancing would be the first thing to relax.”

“The results suggest exactly what the CDC is doing, that ventilation systems and mask usage are most important for preventing transmission and that social distancing would be the first thing to relax,” the researcher says.

When comparing the two models, the researchers found that Wells-Riley and Computational Fluid Dynamics generated similar results, especially in the non-ventilated scenario, but that Wells-Riley underpredicted infection probability by about 29 percent in the ventilated scenario.

As a result, they recommend some of the additional complex effects captured in Computational Fluid Dynamics be applied to Wells-Riley to develop a more complete understanding of risk of infection in a space, says Aaron Foster, a doctoral student in UCF’s Department of Mechanical and Aerospace Engineering and the study’s lead author.

“While the detailed Computational Fluid Dynamics results provided new insights into the risk variation and distance relationships, they also validated the more commonly used Wells-Riley models as capturing the majority of the benefit of ventilation with reasonable accuracy,” Foster says. “This is important since these are publicly available tools that anyone can use to reduce risk.”

The research is part of a larger overall effort to control airborne disease transmission and better understand factors related to being a super-spreader. The researchers are also testing the effects of masks on aerosol and droplet transmission distance. The work is funded in part by the National Science Foundation.

Kinzel received his doctorate in aerospace engineering from Pennsylvania State University and joined UCF in 2018. In addition to being a member of UCF’s Department of Mechanical and Aerospace engineering, a part of UCF’s College of Engineering and Computer Science, he also works with UCF’s Center for Advanced Turbomachinery and Energy Research.

Featured image: These results corroborate recent guidelines from the U.S. Centers for Disease Control and Prevention that recommend reducing social distancing in elementary schools from six to three feet when mask use is universal, study co-author Michael Kinzel says. © University of Central Florida

Reference: Aaron Foster and Michael Kinzel, “Estimating COVID-19 exposure in a classroom setting: A comparison between mathematical and numerical models”, Physics of Fluids 33, 021904 (2021); https://doi.org/10.1063/5.0040755

Provided by University of Central Florida

High Expression of Cell Death Genes Associated With Early Death From Lung Cancer (Medicine)

Patients with a high number of genes most associated with pathways that lead to cell death in lung cancer are at increased risk of dying early from their disease, researchers report.

Also seemingly paradoxically, patients with high expression of this “21-gene cell death signature” the researchers have identified, have indicators that their immune system is attacking the cancer, like higher levels of cytotoxic T cells, which typically kill cancer.

But they also have high levels of molecules that can suppress those T cells, helping transform them into dysfunctional, “exhausted” T cells, they report in the journal Cancers.

This novel genomic signature can be used both to better predict how a patient with lung cancer will do and, more importantly, to better tailor treatments to improve patient survival, says Dr. Ravindra Kolhe, director of the Georgia Esoteric and Molecular (GEM) Laboratory, and vice chair for translational research in the Medical College of Georgia Department of Pathology.

“Immunotherapy is a great approach to treatment but it’s not going to be effective in everyone, and we think this will help identify at the point of diagnosis which immunotherapy will benefit a patient the most,” says Kolhe, the study’s corresponding author.

For example, cancer cells use immune checkpoints, like the protein PD-L1, which normally protects our own cells from being attacked by the immune system, to shield themselves from T cells. The study found a compromised immune function in the tumor microenvironment of patients with the highest cell death index. That means those patients should benefit from immune checkpoint inhibitors like PD-L1 inhibitors, to better enable the immune system to attack their cancer, Kolhe says.

To find a way to improve patient survival, they started by looking at how cells die in this cancer.

Millions of cells die daily and the ways they die include so-called programmed cell death, including apoptosis, in which cells commit suicide because, for example, they have a mutation that cannot be repaired that might cause cancer; and autophagy, where cells basically consume themselves, because of a problem like a malfunctioning component. The more passive, unplanned death is necrosis, where cells might die because of injury. The immune system naturally works through these genes and pathways to kill off invaders and so do cancer treatments like chemotherapy and immunotherapy.

They looked at retrospective data on 510 patients with lung cancer from the national Cancer Genome Atlas, a joint effort of the National Cancer Institute and National Human Genome Research Institute. Genes involved in the different modes of cell death in these patients were assessed, and the researchers found 21 genes occurred most often. They identified 59 individuals with the highest expression and 49 with the lowest expression of these most prominent cell death genes. They also looked at key indicators of immune system activity and compared overall survival, disease-free survival and disease-specific survival in those two groups.

While a prospective study is still needed, Kolhe hopes the cell death index that emerged, will soon give patients with lung cancer, at the time of their diagnosis, the same benefits that good prognostic markers today provide patients with breast cancer.

Lung cancer is the third most common cancer in the United States and the leading cause of cancer death among men and women, according to the Centers for Disease Control and Prevention.

The Food and Drug Administration approved the first lung cancer specific immunotherapy in 2015 and more are currently in clinical trials. Standard lung cancer treatment has included surgery, chemotherapy and radiation with immunotherapy a more recent adjunct, that has helped patients with advanced lung cancer live longer, according to the Cancer Research Institute.

In their early assessment of patients, molecular and genetic pathologists like Kolhe also routinely run a panel for a handful of genes known to drive lung cancer, like EGFR, a protein on the cell surface that normally helps cells grow and divide. In the most common lung cancer type, non-small cell lung cancer, which Kolhe looked at in this study, there can be mutations in EGFR which result, for example, in a lot more of the protein which enables rapid cancer cell growth, and there are inhibitors that block some of these mutations at least for a time.

Featured image: Dr. Ravindra Kolhe (foreground) and Dr. Pankaj Ahluwalia, research associate and the study’s first author. © Kim Ratliff, Augusta University

Reference: Pankaj Ahluwalia, Meenakshi Ahluwalia, […], and Ravindra Kolhe, “Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer”, MDPI, 2021. Read the full study.

Provided by Medical College of Georgia at Augusta University

Researchers Extend the Life of a Dipolar Molecule (Chemistry)

Static, long-lasting molecules are key to molecule-based quantum simulation and information processing

In 2018, Kang-Kuen Ni and her lab earned the cover of Science with an impressive feat: They took two individual atoms, a sodium and a cesium, and forged them into a single dipolar molecule, sodium cesium.

Sodium and cesium normally ignore each other in the wild; but in the Ni lab’s carefully calibrated vacuum chamber, she and her team captured each atom using lasers and then forced them to react, a capability that gifted scientists with a new method to study one of the most basic and ubiquitous processes on Earth: the formation of a chemical bond. With Ni’s invention, scientists could not only discover more about our chemical underpinnings, they could start creating bespoke molecules for novel uses like qubits for quantum computers.

But there was one flaw in their original sodium cesium molecule: “That molecule was lost soon after it’s made,” said Ni, the Morris Kahn associate professor of chemistry and chemical biology and of physics. Now, in a new study published in Physics Review Letters, Ni and her team report a new feat: They granted their molecule an extended lifetime of up to almost three and a half seconds—a luxury of time in the quantum realm—by controlling all the degrees of freedom (including its motion) of an individual dipolar molecule for the first time. During those precious seconds, the researchers can maintain the full quantum control necessary for stable qubits, the building blocks for a wide variety of exciting quantum applications.

The above diagram shows part of the molecular assembly process from individually trapped atoms to ground state molecule using optical tweezers (lasers). Photo courtesy of the Ni group

According to the paper, “These long-lived, fully quantum state-controlled individual dipolar molecules provide a key resource for molecule-based quantum simulation and information processing.” For example, such molecules could accelerate progress toward quantum simulation of new phases of matter (faster than any known computer), high-fidelity quantum information processing, precision measurements, and basic research in the field of cold chemistry (one of Ni’s specialties).

And, by forming obedient molecules in their quantum ground states (basically, their simplest, most pliant form), the researchers created more reliable qubits with electric handles, which, like the magnetic handles of a magnet, allow researchers to interact with them in new ways (for example, with microwaves and electric fields).

Next, the team is working on scaling their process: They plan to assemble not just one molecule from two atoms but force larger collections of atoms to interact and form molecules in parallel. In so doing, they can also start to perform long-range entanglement interactions between molecules, the basis for information transfer in quantum computing.

“With the addition of microwave and electric field control,” said Ni, “molecular qubits for quantum computing applications and simulations that further our understanding of quantum phases of matter are within experimental reach.”

This work is supported, in part, by the National Science Foundation, the Air Force Office of Scientific Research, and the Camille and Henry Dreyfus Foundation.

Featured image: Kang-Kuen Ni (Right) and Yu Liu (Left) looking at their ultracold technology © Harvard University

Reference: William B. Cairncross, Jessie T. Zhang, Lewis R. B. Picard, Yichao Yu, and Kenneth Wang, “Assembly of a Rovibrational Ground State Molecule in an Optical Tweezer”, Phys. Rev. Lett. 126, 123402 – Published 26 March 2021. https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.126.123402

Provided by Harvard University

Like Peas in a Pod: UVA Astronomer’s Survey of Young Stars Published (Astronomy)

An international research group led by a postdoctoral fellow in the University of Virginia’s Department of Astronomy identified a rich organic chemistry in young disks surrounding 50 newly formed stars.

Relying on observations from the Atacama Large Millimeter/submillimeter Array telescope in Chile – known as ALMA – the findings offer astronomers a greater understanding of the mechanisms responsible for the formation of organic molecules in space, at the dawn of planet formation.

The variety of organic molecules identified also raises an important question for astronomers: How common is the chemical heritage of these disks? Since disks around young stars are known to be the sites of future planet formation, understanding their prebiotic potential is key. The findings of the Star and Planet Formation Laboratory of Japan’s RIKEN Cluster for Pioneering Research were published March 23 by the American Astronomical Society in The Astrophysical Journal.

Yao-Lun Yang is lead author of the paper and a postdoctoral fellow at UVA, based in the Department of Astronomy. (Contributed photo)

“This research is going to help us test our current knowledge about the chemical evolution ongoing in the disks of newly formed stars,” said Yao-Lun Yang, lead author of the paper and an Origins postdoctoral fellow with the Virginia Initiative on Cosmic Origins, based in UVA’s Department of Astronomy. Yang was a Japan Society for the Promotion of Science fellow at RIKEN, a national science research institute in Japan when he began work on the project with other researchers affiliated with RIKEN, the University of Tokyo, France’s Institut de Planétologie et d’Astrophysique de Grenoble, and other institutions.

“We surveyed the chemical composition of the material where these protoplanetary disks and planets grow from, and what we found quite interesting were the range of complex molecules we observed,” Yang said. “Even where we observed a wide range of total amounts of specific organic molecules, we still found a similar chemical pattern among the different regions we studied.”

Studying the Perseus Molecular Cloud

A collection of gas and dust over 500 light-years across, the Perseus Molecular Cloud hosts an abundance of young stars. (Photo courtesy NASA/JPL-Caltech)

Stars form from interstellar clouds, which consist of gas and dust, via gravitational contraction. These young stars are surrounded by disks, which have the potential to evolve into planetary systems. Identifying the initial chemical composition of these forming disks may offer clues to the origins of planets like Earth, Yang said.

The RIKEN-based research focused on 50 sources embedded in the Perseus molecular cloud, which contains young protostars with protoplanetary disks forming around them. Even with the power of the ALMA telescope, it took more than three years, over the course of several projects, to complete the survey. By observing the emission emitted by molecules at specific frequencies, the team studied the amount of methanol, acetonitrile, methyl formate, dimethyl ether, and larger organics – an unprecedented survey of “complex” organic molecules within a large sample of solar-type young stars.

According to the survey, 58% of the sources contained large organic molecules, while 42% of the sources exhibited no sign of them. Surprisingly, the total amount of any given molecule measured showed a wide variety, more than 100 times difference, even for such similar stars. Some sources proved to be rich in organic molecules, even if they had relatively little material surrounding the protostar. Others featured few organic properties, despite a large amount of material surrounding the protostar. Nonetheless, the relative quantities were remarkably similar. 

The fact that some systems have substantially more or less total organic content suggests that the evolutionary history of the local environment may have a critical impact to the molecular composition in the resultant planetary systems. While the chemical patterns between systems appear to be relatively similar, some disks may “luck out” with more organic richness compared to others.

Such questions hopefully will be answered in the future through efforts to follow the organic reservoir over time by expanding surveys to even younger or much older systems, Yang said.

Featured image: An aerial view of the Chajnantor Plateau, located at an altitude of 5,000 meters in the Chilean Andes, where the array of ALMA antennas is located. (Photo courtesy Clem & Adri Bacri-Normier (wingsforscience.com)/ESO)

Reference: Yao-Lun Yang et al. The Perseus ALMA Chemistry Survey (PEACHES). I. The Complex Organic Molecules in Perseus Embedded Protostars, The Astrophysical Journal (2021). DOI: 10.3847/1538-4357/abdfd6

Provided by University of Virginia

New Study Ties Solar Variability To The Onset Of Decadal La Nina Events (Planetary Science)

Authors apply a 22-year solar clock to find an elusive correlation

A new study shows a correlation between the end of solar cycles and a switch from El Nino to La Nina conditions in the Pacific Ocean, suggesting that solar variability can drive seasonal weather variability on Earth. 

If the connection outlined in the journal Earth and Space Science holds up, it could significantly improve the predictability of the largest El Nino and La Nina events, which have a number of seasonal climate effects over land. For example, the southern United States tends to be warmer and drier during a La Nina, while the northern U.S. tends to be colder and wetter.

“Energy from the Sun is the major driver of our entire Earth system and makes life on Earth possible,” said Scott McIntosh, a scientist at the National Center for Atmospheric Research (NCAR) and co-author of the paper. “Even so, the scientific community has been unclear on the role that solar variability plays in influencing weather and climate events here on Earth. This study shows there’s reason to believe it absolutely does and why the connection may have been missed in the past.”

The study was led by Robert Leamon at the University of Maryland-Baltimore County, and it is also co-authored by Daniel Marsh at NCAR. The research was funded by the National Science Foundation, which is NCAR’s sponsor, and the NASA Living With a Star program. 


The appearance (and disappearance) of spots on the Sun — the outwardly visible signs of solar variability — have been observed by humans for hundreds of years. The waxing and waning of the number of sunspots takes place over approximately 11-year cycles, but these cycles do not have distinct beginnings and endings. This fuzziness in the length of any particular cycle has made it challenging for scientists to match up the 11-year cycle with changes happening on Earth.

In the new study, the researchers rely on a more precise 22-year “clock” for solar activity derived from the Sun’s magnetic polarity cycle, which they outlined as a more regular alternative to the 11-year solar cycle in several companion studies published recently in peer-reviewed journals. 

The 22-year cycle begins when oppositely charged magnetic bands that wrap the Sun appear near the star’s polar latitudes, according to their recent studies. Over the cycle, these bands migrate toward the equator — causing sunspots to appear as they travel across the mid-latitudes. The cycle ends when the bands meet in the middle, mutually annihilating one another in what the research team calls a terminator event. These terminators provide precise guideposts for the end of one cycle and the beginning of the next.

The researchers imposed these terminator events over sea surface temperatures in the tropical Pacific stretching back to 1960. They found that the five terminator events that occurred between that time and 2010-11 all coincided with a flip from an El Nino (when sea surface temperatures are warmer than average) to a La Nina (when the sea surface temperatures are cooler than average). The end of the most recent solar cycle — which is unfolding now — is also coinciding with the beginning of a La Nina event. 

“We are not the first scientists to study how solar variability may drive changes to the Earth system,” Leamon said. “But we are the first to apply the 22-year solar clock. The result — five consecutive terminators lining up with a switch in the El Nino oscillation — is not likely to be a coincidence.”

In fact, the researchers did a number of statistical analyses to determine the likelihood that the correlation was just a fluke. They found there was only a 1 in 5,000 chance or less (depending on the statistical test) that all five terminator events included in the study would randomly coincide with the flip in ocean temperatures. Now that a sixth terminator event — and the corresponding start of a new solar cycle in 2020 — has also coincided with an La Nina event, the chance of a random occurrence is even more remote, the authors said. 

The paper does not delve into what physical connection between the Sun and Earth could be responsible for the correlation, but the authors note that there are several possibilities that warrant further study, including the influence of the Sun’s magnetic field on the amount of cosmic rays that escape into the solar system and ultimately bombard Earth. However, a robust physical link between cosmic rays variations and climate has yet to be determined. 

“If further research can establish that there is a physical connection and that changes on the Sun are truly causing variability in the oceans, then we may be able to improve our ability to  predict El Nino and La Nina events,” McIntosh said.

Featured image: A solar flare on the surface of the Sun © NASA


Title: Termination of Solar Cycle and Correlated Tropospheric Variability
Authors: Robert J. Leamon, Scott W. McIntosh, and Daniel R. Marsh
Journal: Earth and Space Science

Provided by UCAR